Crosstalk between HDAC6 and Nox2-based NADPH oxidase mediates HIV-1 Tat-induced pro-inflammatory responses in astrocytes

Redox Biology
Gi Soo YounJinseu Park

Abstract

Histone deacetylase 6 (HDAC6) likely is important in inflammatory diseases. However, how HDAC6 exerts its effect on inflammatory processes remains unclear. HIV-1 transactivator of transcription (Tat) activates NADPH oxidase resulting in generation of reactive oxygen species (ROS), leading to extensive neuro-inflammation in the central nervous system. We investigated the correlation of HDAC6 and NADPH oxidase in HIV-1 Tat-stimulated astrocytes. HDAC6 knockdown attenuated HIV-1 Tat-induced ROS generation and NADPH oxidase activation. HDAC6 knockdown suppressed HIV-1 Tat-induced expression of NADPH oxidase subunits, such as Nox2, p47phox, and p22phox. Specific inhibition of HDAC6 using tubastatin A suppressed HIV-1 Tat-induced ROS generation and activation of NADPH oxidase. N-acetyl cysteine, diphenyl iodonium, and apocynin suppressed HIV-1 Tat-induced expression of HDAC6 and the pro-inflammatory chemokines CCL2, CXCL8, and CXCL10. Nox2 knockdown attenuated HIV-1 Tat-induced HDAC6 expression and subsequent expression of chemokines. The collective results point to the potential crosstalk between HDAC6 and NADPH oxidase, which could be a combined therapeutic target for relief of HIV-1 Tat-mediated neuro-inflammation.

Citations

Dec 20, 2017·Molecular and Cellular Biochemistry·Nikhat SaleemShyamal K Goswami
Sep 27, 2018·Frontiers in Microbiology·Lin ChenChristian Schölz
Jun 26, 2020·Frontiers in Aging Neuroscience·Jamie MarinoMichael R Nonnemacher
Jun 27, 2019·Journal of Molecular Neuroscience : MN·Hriday Shanker Pandey, Pankaj Seth
Jun 25, 2020·Cellular and Molecular Life Sciences : CMLS·Jamie MarinoMichael R Nonnemacher
Oct 9, 2020·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Shilpa BuchAshutosh Tripathi

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Methods Mentioned

BETA
electrophoresis
PCR
ELISA
co-immunoprecipitation
transfection
fluorescence microscopy
GTPase

Software Mentioned

SYSTAT
SigmaPlot

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